Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27−IgD−) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). Cartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.

中文翻译：

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早期类风湿关节炎患者的软骨破坏与 CD21−/低双阴性 B 细胞相关

疾病特异性自身抗体的存在以及针对 B 细胞的治疗效果支持 B 细胞参与类风湿性关节炎 (RA) 的发病机制。表达低水平或缺乏 B 细胞受体 (BCR) 辅助受体 CD21、CD21−/低 B 细胞的 B 细胞与自身免疫性疾病（包括 RA）有关。在这项研究中，我们对新诊断的早期 RA (eRA) 患者的 CD21+ 和 CD21−/低 B 细胞亚群进行了表征，并研究了是否有任何 B 细胞亚群与自身抗体状态、疾病活动性和/或关节破坏相关。招募了 76 名 eRA 患者和 28 名年龄和性别匹配的健康捐献者。评估了多种临床参数，包括疾病活动性和放射学关节破坏。使用流式细胞术分析外周血 (PB) 和滑液 (SF) 中的 B 细胞亚群。与健康捐献者相比，eRA 患者的 PB 中幼稚 CD21+ B 细胞的频率较高。在记忆 B 细胞中，eRA 患者 CD21+CD27+ 亚群和 CD21−/低 CD27+IgD+ 亚群的频率较低。唯一发现与临床因素相关的 B 细胞亚群是 CD21−/低双阴性（DN、CD27−IgD−）细胞群，与关节间隙狭窄评分（即软骨破坏）相关。此外，在确诊 RA 患者的 SF 中，CD21−/低 DN B 细胞扩增，这些细胞表达核因子 κB 配体 (RANKL) 的受体激活剂。eRA 患者的软骨破坏与 PB 中 CD21−/低 DN B 细胞比例增加相关。该子集也在已确诊的 RA 患者的 SF 中进行了扩展，并表达 RANKL。综上所述，我们的结果表明 CD21−/低 DN 在 RA 发病机制中发挥作用。